Primary immunodeficiency or monogenic inflammatory bowel disease

Gene: LYN

Green List (high evidence)

The rating of this gene has been updated to green and the mode of inheritance updated to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.

Created: 3 May 2024, 8:36 p.m. | Last Modified: 3 May 2024, 8:36 p.m.

Panel Version: 5.3

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Green List (high evidence)

Comment on list classification: There is sufficient evidence available (four unrelated cases and functional studies) for the promotion of this gene to green rating in the next GMS review.

Created: 2 Jan 2024, 2:40 p.m. | Last Modified: 2 Jan 2024, 2:40 p.m.

Panel Version: 4.130

As reviewed by Boaz Palterer, there are four unrelated patients reported with systemic autoinflammatory disorder (SAID) and identified with de novo LYN variants. Of these one patient was reported in PMID:36122175 and three unrelated boys were reported in PMID:36932076. The patient data was also supported by functional evidence, which suggested gain of function mechanism for LYN variants.

This gene was associated with relevant phenotypes in OMIM (MIM #620376), but not yet in Gene2Phenotype.

Created: 2 Jan 2024, 2:37 p.m. | Last Modified: 2 Jan 2024, 2:37 p.m.

Panel Version: 4.125

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Autoinflammatory disease, systemic, with vasculitis, OMIM:620376

Publications

• 36122175
• 36932076

Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments

Green List (high evidence)

Louvrier et al. described 1 patient ( PMID 36122175 ) and De Jesus et al ( https://www.medrxiv.org/content/10.1101/2022.09.27.22280319v1.full.pdf ) 3 additional patients, for a total of 4 kindreds with de novo LYN mutations.
Strong functional evidence: p.Tyr508His, p.Tyr508Phe and p.Tyr508* cause inhibition loss, leading to Tyr397 autophosphorylation and functional GOF.
Sources: Literature

Created: 3 Oct 2022, 4 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Autoinflammatory; Neutrophilic vasculitis; Liver fibrosis; Chronic urticaria; Atopic dermatitis; Fever

Publications

• 36122175